Biology subjects

Alkislar, I.

Publications and source records attributed to Alkislar, I..

5 recordsLinked to original sources

bioRxiv2026

Reciprocal control of the stomach and intestine by viscerosensory neurons in caudal brainstem

Digestion requires precisely timed transit of food through the gastrointestinal tract. Here we show that emptying of food from the stomach occurs in discrete pulses, separated by pauses that allow the proximal duodenum to clear before the next bolus arrives. By combining X-ray fluoroscopy of the gut with calcium imaging of the brainstem, we identify a population of neurons defined by expression of neuropeptide FF (NPFF) that tracks these duodenal dynamics. Stimulation of NPFF neurons induces a coordinated response that inhibits gastric emptying and accelerates intestinal transit, thereby clearing the proximal intestine for the next bolus of food. These neurons also bidirectionally control food intake through cholinergic signaling in the gut. These findings reveal a mechanism by which brainstem transforms the sensory detection of nutrients in the duodenum into the opposing control of the stomach and intestine. They also establish an experimental approach for dissecting gut-brain signaling in behaving animals.

neuroscience↗

bioRxiv2025

Fast-conducting mechanonociceptors uniquely engage reflexive and affective pain circuitry to drive protective responses

Nociceptors detect damaging stimuli and evoke pain in healthy animals. We conducted an optogenetic activation screen to identify genetically defined nociceptor populations that elicit place aversion and nocifensive behaviors in response to stimulation. Smr2Cre- and Bmpr1bCre-labeled A{delta} high-threshold mechanoreceptors (HTMRs) emerged as two of the few nociceptor populations, and we focused on investigating their physiological, morphological, functional, and synaptic properties. These neurons densely innervate skin and other organs, are activated only by intense, potentially damaging stimuli, and are necessary for protective responses to sharp mechanical stimuli. Centrally, A{delta}-HTMRs projections span multiple spinal segments and terminate across spinal cord laminae, forming strong, monosynaptic connections onto anterolateral tract projection neurons, including antenna cells of the deep dorsal horn. A{delta}-HTMRs also engage a local spinal reflex circuit enabling a remarkably rapid limb withdrawal. Thus, A{delta}-HTMRs are myelinated nociceptors with unique properties that can be exploited for development of new analgesics.

neuroscience↗

bioRxiv2023

The developmental timing of spinal touch processing alterations and its relation to ASD-associated behaviors in mouse models

Altered somatosensory reactivity is frequently observed among individuals with autism spectrum disorders (ASDs). Here, we report that while multiple mouse models of ASD exhibit aberrant somatosensory behaviors in adulthood, some models exhibit altered tactile reactivity as early as embryonic development, while in others, altered reactivity emerges later in life. Additionally, tactile over-reactivity during neonatal development is associated with anxiety-like behaviors and social interaction deficits in adulthood, whereas tactile over-reactivity that emerges later in life is not. The locus of circuit disruption dictates the timing of aberrant tactile behaviors: altered feedback or presynaptic inhibition of peripheral mechanosensory neurons leads to abnormal tactile reactivity during neonatal development, while disruptions in feedforward inhibition in the spinal cord lead to touch reactivity alterations that manifest later in life. Thus, the developmental timing of aberrant touch processing can predict the manifestation of ASD-associated behaviors in mouse models, and differential timing of sensory disturbance onset may contribute to phenotypic diversity across individuals with ASD.

neuroscience↗

bioRxiv2022

Pathway-specific inputs to the superior colliculus support flexible triggering of innate behaviors

Behavioral flexibility requires the ability to modify the feedforward transmission of sensory information. The superior colliculus mediates visually guided innate defensive behaviors via cell-type specific projections. However, how brain-wide inputs to the superior colliculus are organized to modulate visual processing and enable flexible behavior remains unknown. To determine these rules, we focused on inhibitory projection (Gad2) neurons. Trans-synaptic tracing and neuronal recordings revealed that Gad2 neurons projecting to the dorsal lateral geniculate nucleus (LGd) and the parabigeminal nucleus (PBG) form two separate anatomical and functional populations, where each circuit received a different set of non-retinal inputs. Inhibiting LGd or PBG projecting Gad2 neurons resulted in opposing effects on behavior; increasing freezing or escape probability to visual looming stimuli, respectively. These data suggest that projection-specific sampling of brain-wide inputs provide a circuit design principle that enables feed-forward transfer of visual threat to be independently adjusted to produce context specific behavior.

neuroscience↗

bioRxiv2021

Mechanoreceptor synapses in the brainstem shape the central representation of touch

Mammals use glabrous (hairless) skin of their hands and feet to navigate and manipulate their environment. Cortical maps of the body surface across species contain disproportionately large numbers of neurons dedicated to glabrous skin sensation, potentially reflecting a higher density of mechanoreceptors that innervate these skin regions. Here, we find that disproportionate representation of glabrous skin emerges over postnatal development at the first synapse between peripheral mechanoreceptors and their central targets in the brainstem. Mechanoreceptor synapses undergo developmental refinement that depends on proximity of their terminals to glabrous skin, such that those innervating glabrous skin make synaptic connections that expand their central representation. In mice that do not sense gentle touch, mechanoreceptors innervating glabrous skin still make more powerful synaptic connections in the brainstem. We propose that the skin region a mechanoreceptor innervates controls refinement of its central synapses over development to shape the representation of touch in the brain.

neuroscience↗